PMID- 34727112 OWN - NLM STAT- MEDLINE DCOM- 20211229 LR - 20211229 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 16 IP - 11 DP - 2021 TI - Mass recovery following caloric restriction reverses lipolysis and proteolysis, but not gluconeogenesis, in insulin resistant OLETF rats. PG - e0252360 LID - 10.1371/journal.pone.0252360 [doi] LID - e0252360 AB - Caloric restriction (CR) is one of the most important behavioral interventions to reduce excessive abdominal adiposity, which is a risk factor for the development of insulin resistance. Previous metabolomics studies have characterized substrate metabolism during healthy conditions; however, the effects of CR and subsequent mass recovery on shifts in substrate metabolism during insulin resistance (IR) have not been widely investigated. To assess the effects of acute CR and the subsequent mass recovery on shifts in substrate metabolism, a cohort of 15-week old Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats were calorie restricted (CR: 50% x 10 days) with or without partial body mass recovery (PR; 73% x 7 days), along with their respective ad libitum controls. End-of-study plasma samples were analyzed for primary carbon metabolites by gas chromatography (GC) time-of-flight (TOF) mass spectrometry (MS) data acquisition. Data analysis included PCA, Pearson correlation vs previously reported variables (adipose and body masses, and insulin resistance index, IRI), and metabolomics maps (MetaMapp) generated for the most significant group comparisons. All treatments elicited a significant group differentiation in at least one principal component. CR improved TCA cycle in OLETF, and increased lipolysis and proteolysis. These changes were reversed after PR except for gluconeogenesis. Plasma lipid concentrations were inversely correlated to IRI in LETO, but not OLETF. These shifts in substrate metabolism suggest that the CR-induced decreases in adipose may not be sufficient to more permanently alter substrate metabolism to improve IR status during metabolic syndrome. FAU - Cornejo, Manuel A AU - Cornejo MA AUID- ORCID: 0000-0002-2446-8674 AD - School of Natural Sciences, University of California, Merced, CA, United States of America. FAU - Dhillon, Jaapna AU - Dhillon J AUID- ORCID: 0000-0003-4798-9111 AD - Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, United States of America. FAU - Nishiyama, Akira AU - Nishiyama A AD - Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan. FAU - Nakano, Daisuke AU - Nakano D AD - Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan. FAU - Ortiz, Rudy M AU - Ortiz RM AD - School of Natural Sciences, University of California, Merced, CA, United States of America. LA - eng SI - figshare/10.6084/m9.figshare.12831005 GR - T37 MD001480/MD/NIMHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20211102 PL - United States TA - PLoS One JT - PloS one JID - 101285081 SB - IM MH - Adipose Tissue/metabolism MH - Animals MH - *Caloric Restriction MH - Gluconeogenesis/*physiology MH - Glucose Tolerance Test MH - Insulin Resistance/*physiology MH - Lipolysis/*physiology MH - Liver/*metabolism MH - Proteolysis MH - Rats MH - Rats, Inbred OLETF PMC - PMC8562784 COIS- The authors have declared that no competing interests exist. EDAT- 2021/11/03 06:00 MHDA- 2021/12/30 06:00 PMCR- 2021/11/02 CRDT- 2021/11/02 17:19 PHST- 2021/05/19 00:00 [received] PHST- 2021/10/18 00:00 [accepted] PHST- 2021/11/02 17:19 [entrez] PHST- 2021/11/03 06:00 [pubmed] PHST- 2021/12/30 06:00 [medline] PHST- 2021/11/02 00:00 [pmc-release] AID - PONE-D-21-11012 [pii] AID - 10.1371/journal.pone.0252360 [doi] PST - epublish SO - PLoS One. 2021 Nov 2;16(11):e0252360. doi: 10.1371/journal.pone.0252360. eCollection 2021.